Safety and Immunogenicity of an mRNA-Based RSV Vaccine Including a 12-Month Booster in a Phase I Clinical Trial in Healthy Older Adults.

BACKGROUND: An mRNA-based RSV vaccine, mRNA-1345, is under clinical investigation to address RSV disease burden in older adults. METHODS: This phase 1, randomized, observer-blind, placebo-controlled, dose-ranging study evaluated safety, reactogenicity, and immunogenicity of mRNA-1345 in adults 65-79 years (NCT04528719). Participants were randomized to receive 1-dose of mRNA-1345 (12.5, 25, 50, 100, or 200-µg) or placebo and matched mRNA-1345 booster or placebo at 12-months. RESULTS: Overall, 298 participants received the first injection; 247 received the 12-month booster injection. mRNA-1345 was generally well-tolerated after both injections, with the most frequently reported solicited adverse reactions being injection-site pain, fatigue, headache, arthralgia, and myalgia. Reactogenicity was higher after the booster injection than the first injection but similar severity, time-to-onset, and duration. A single mRNA-1345 injection boosted RSV-A and RSV-B neutralizing antibody titers (nAb) and prefusion-F-binding antibody (preF-bAb) concentrations at 1-month (geometric mean-fold rises: RSV-A, 10.2-16.5; RSV-B, 5.3-12.5; preF-bAb, 7.2-12.1). RSV antibody levels remained above baseline through 12-months, indicating immune persistence. A 12-month booster injection also increased RSV-A and RSV-B nAb titers and preF-bAb concentrations; titers post-booster injection were numerically lower compared to titers after the first-dose, with overlapping 95% CIs. CONCLUSIONS: mRNA-1345 was well-tolerated and immunogenic following a single injection and a 12-month booster. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04528719.

Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults.

BACKGROUND: Respiratory syncytial virus (RSV) can cause substantial morbidity and mortality among older adults. An mRNA-based RSV vaccine, mRNA-1345, encoding the stabilized RSV prefusion F glycoprotein, is under clinical investigation. METHODS: In this ongoing, randomized, double-blind, placebo-controlled, phase 2-3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive one dose of mRNA-1345 (50 µg) or placebo. The two primary efficacy end points were the prevention of RSV-associated lower respiratory tract disease with at least two signs or symptoms and with at least three signs or symptoms. A key secondary efficacy end point was the prevention of RSV-associated acute respiratory disease. Safety was also assessed. RESULTS: Overall, 35,541 participants were assigned to receive the mRNA-1345 vaccine (17,793 participants) or placebo (17,748). The median follow-up was 112 days (range, 1 to 379). The primary analyses were conducted when at least 50% of the anticipated cases of RSV-associated lower respiratory tract disease had occurred. Vaccine efficacy was 83.7% (95.88% confidence interval [CI], 66.0 to 92.2) against RSV-associated lower respiratory tract disease with at least two signs or symptoms and 82.4% (96.36% CI, 34.8 to 95.3) against the disease with at least three signs or symptoms. Vaccine efficacy was 68.4% (95% CI, 50.9 to 79.7) against RSV-associated acute respiratory disease. Protection was observed against both RSV subtypes (A and B) and was generally consistent across subgroups defined according to age and coexisting conditions. Participants in the mRNA-1345 group had a higher incidence than those in the placebo group of solicited local adverse reactions (58.7% vs. 16.2%) and of systemic adverse reactions (47.7% vs. 32.9%); most reactions were mild to moderate in severity and were transient. Serious adverse events occurred in 2.8% of the participants in each trial group. CONCLUSIONS: A single dose of the mRNA-1345 vaccine resulted in no evident safety concerns and led to a lower incidence of RSV-associated lower respiratory tract disease and of RSV-associated acute respiratory disease than placebo among adults 60 years of age or older. (Funded by Moderna; ConquerRSV ClinicalTrials.gov number, NCT05127434.).

The Annual Economic Burden of Respiratory Syncytial Virus in Adults in the United States.

BACKGROUND: Current estimates of the economic burden of respiratory syncytial virus (RSV) are needed for policymakers to evaluate adult RSV vaccination strategies. METHODS: A cost-of-illness model was developed to estimate the annual societal burden of RSV in US adults aged ≥60 years. Additional analyses were conducted to estimate the burden of hospitalized RSV in all adults aged 50-59 years and in adults aged 18-49 years with potential RSV risk factors. RESULTS: Among US adults aged ≥60 years, the model estimated 4.0 million annual RSV cases (95% UI, 2.7-5.6 million) and an annual economic burden of $6.6 billion (95% UI, $3.1-$12.9 billion; direct medical costs, $2.9 billion; indirect costs, $3.7 billion). The 4% of RSV cases that were hospitalized contributed to 94% of direct medical costs. Additional analyses estimated $422 million in annual hospitalization costs among all adults aged 50-59 years. Among adults aged 18-49 years with RSV risk factors, annual per capita burden was highest among people with congestive heart failure at $51,100 per 1000 people. DISCUSSION: The economic burden of RSV is substantial among adults aged ≥50 years, and among adults aged 18-49 years with RSV risk factors, underscoring the need for preventive interventions for these populations.

Characterizing U.S. mothers with high human papillomavirus vaccine intent yet unvaccinated adolescents.

HPV vaccination rates remain suboptimal in the United States. While the current literature focuses on expressly hesitant parents, few studies have examined parents with "high intent", or those indicating they definitely will vaccinate and have had the opportunity but not yet vaccinated their adolescents. Our objective was to differentiate characteristics of mothers with high intent from those who already vaccinated their adolescents using various socioeconomic, previous vaccine decision-making, and healthcare provider relationship-related variables. English-speaking mothers or female guardians of adolescents ages 11-14 years living in low HPV vaccine uptake states within the U.S. in September 2018 were recruited from a national survey panel as part of a larger study. We assessed HPV vaccine status of their adolescents and categorized respondents into two categories: Already Vaccinated and High Intent. We assessed differences using a multivariable logistic regression model. Among 2406 mothers, 18% reported high intent vs. 82% already having vaccinated. Mothers with high intent were more likely to identify as non-Hispanic White (p = 0.01), to have a younger adolescent (p < 0.001), and to report not receiving a provider HPV vaccination recommendation (p < 0.001). Mothers who estimated that half/more (vs. less) of their child's friends have received/will receive the vaccine had higher odds of already vaccinating (p < 0.001). Our findings suggest that clinicians may be able to improve HPV vaccination uptake within their practices by giving repeated, high-quality recommendations to parents of children who are not yet vaccinated. Additionally, these findings indicate perceived social norms may play a large role in on-time vaccine uptake. Reassuring hesitant parents that most parents accept the vaccine may also improve uptake in clinical practice.

Who gets treated for influenza: A surveillance study from the US Food and Drug Administration's Sentinel System.

OBJECTIVE: We describe the baseline characteristics and complications of individuals with influenza in the US FDA's Sentinel System by antiviral treatment timing. DESIGN: Retrospective cohort design. PATIENTS: Individuals aged ≥6 months with outpatient diagnoses of influenza in June 2014-July 2017, 3 influenza seasons. METHODS: We identified the comorbidities, vaccination history, influenza testing, and outpatient antiviral dispensings of individuals with influenza using administrative claims data from 13 data partners including the Centers for Medicare and Medicaid Services, integrated delivery systems, and commercial health plans. We assessed complications within 30 days: hospitalization, oxygen use, mechanical ventilation, critical care, ECMO, and death. RESULTS: There were 1,090,333 influenza diagnoses in 2014-2015; 1,005,240 in 2016-2017; and 578,548 in 2017-2018. Between 49% and 55% of patients were dispensed outpatient treatment within 5 days. In all periods >80% of treated individuals received treatment on the day of diagnosis. Those treated on days 1-5 after diagnosis had higher prevalences of diabetes, chronic obstructive pulmonary disease, asthma, and obesity compared to those treated on the day of diagnosis or not treated at all. They also had higher rates of hospitalization, oxygen use, and critical care. In 2014-2015, among those aged ≥65 years, the rates of hospitalization were 45 per 1,000 diagnoses among those treated on day 0; 74 per 1,000 among those treated on days 1-5; and 50 per 1,000 among those who were untreated. CONCLUSIONS: In a large, national analysis, approximately half of people diagnosed with influenza in the outpatient setting were treated with antiviral medications. Delays in outpatient dispensed treatment were associated with higher prevalence of comorbidities and higher rates of complication.

BBCIC Research Network Analysis of First-Cycle Prophylactic G-CSF Use in Patients Treated With High-Neutropenia Risk Chemotherapy.

BACKGROUND: Chemotherapy-induced febrile neutropenia (FN) is prevented or minimized with granulocyte colony-stimulating factors (G-CSFs). Several G-CSF biosimilars are approved in the United States. The Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) is a nonprofit initiative whose objective is to provide scientific evidence on real-world use and comparative safety and effectiveness of biologics and biosimilars using the BBCIC distributed research network (DRN). PATIENTS AND METHODS: We describe real-world G-CSF use in patients with breast or lung cancer receiving first-cycle chemotherapy associated with high FN risk. We assessed hospitalizations for FN, availability of absolute neutrophil counts, and G-CSF-induced adverse events to inform future observational comparative effectiveness studies of G-CSF reference products and their biosimilars. A descriptive analysis of 5 participating national health insurance plans was conducted within the BBCIC DRN. RESULTS: A total of 57,725 patients who received at least one G-CSF dose were included. Most (92.5%) patients received pegfilgrastim. FN hospitalization rates were evaluated by narrow (<0.5%), intermediate (1.91%), and broad (2.99%) definitions. Anaphylaxis and hyperleukocytosis were identified in 1.15% and 2.28% of patients, respectively. This analysis provides real-world evidence extracted from a large, readily available database of diverse patients, characterizing G-CSF reference product use to inform the feasibility of future observational comparative safety and effectiveness analyses of G-CSF biosimilars. We showed that the rates of FN and adverse events in our research network are consistent with those reported by previous small studies. CONCLUSIONS: Readily available BBCIC DRN data can be used to assess G-CSF use with the incidence of FN hospitalizations. Insufficient laboratory result data were available to report absolute neutrophil counts; however, other safety data are available for assessment that provide valuable baseline data regarding the effectiveness and safety of G-CSFs in preparation for comparative effectiveness studies of reference G-CSFs and their biosimilars.

Vaccine Safety Datalink infrastructure enhancements for evaluating the safety of maternal vaccination.

BACKGROUND: Identifying pregnancy episodes and accurately estimating their beginning and end dates are imperative for observational maternal vaccine safety studies using electronic health record (EHR) data. METHODS: We modified the Vaccine Safety Datalink (VSD) Pregnancy Episode Algorithm (PEA) to include both the International Classification of Disease, ninth revision (ICD-9 system) and ICD-10 diagnosis codes, incorporated additional gestational age data, and validated this enhanced algorithm with manual medical record review. We also developed the new Dynamic Pregnancy Algorithm (DPA) to identify pregnancy episodes in real time. RESULTS: Around 75% of the pregnancy episodes identified by the enhanced VSD PEA were live births, 12% were spontaneous abortions (SABs), 10% were induced abortions (IABs), and 0.4% were stillbirths (SBs). Gestational age was identified for 99% of live births, 89% of SBs, 69% of SABs, and 42% of IABs. Agreement between the PEA-assigned and abstractor-identified pregnancy outcome and outcome date was 100% for live births, but was lower for pregnancy losses. When gestational age was available in the medical record, the agreement was higher for live births (97%), but lower for pregnancy losses (75%). The DPA demonstrated strong concordance with the PEA and identified pregnancy episodes ⩾6 months prior to the outcome date for 89% of live births. CONCLUSION: The enhanced VSD PEA is a useful tool for identifying pregnancy episodes in EHR databases. The DPA improves the timeliness of pregnancy identification and can be used for near real-time maternal vaccine safety studies. PLAIN LANGUAGE SUMMARY: Improving identification of pregnancies in the Vaccine Safety Datalink electronic medical record databases to allow for better and faster monitoring of vaccination safety during pregnancy Introduction: It is important to monitor of the safety of vaccines after they have been approved and licensed by the Food and Drug Administration, especially among women vaccinated during pregnancy. The Vaccine Safety Datalink (VSD) monitors vaccine safety through observational studies within large databases of electronic medical records. Since 2012, VSD researchers have used an algorithm called the Pregnancy Episode Algorithm (PEA) to identify the medical records of women who have been pregnant. Researchers then use these medical records to study whether receiving a particular vaccine is linked to any negative outcomes for the woman or her child.Methods: The goal of this study was to update and enhance the PEA to include the full set of medical record diagnostic codes [both from the older International Classification of Disease, ninth revision (ICD-9 system) and the newer ICD-10 system] and to incorporate additional sources of data about gestational age. To ensure the validity of the PEA following these enhancements, we manually reviewed medical records and compared the results with the algorithm. We also developed a new algorithm, the Dynamic Pregnancy Algorithm (DPA), to identify women earlier in pregnancy, allowing us to conduct more timely vaccine safety assessments.Results: The new version of the PEA identified 2,485,410 pregnancies in the VSD database. The enhanced algorithm more precisely estimated the beginning of pregnancies, especially those that did not result in live births, due to the new sources of gestational age data.Conclusion: Our new algorithm, the DPA, was successful at identifying pregnancies earlier in gestation than the PEA. The enhanced PEA and the new DPA will allow us to better evaluate the safety of current and future vaccinations administered during or around the time of pregnancy.

Efficacy of tailored messages to improve behavioral intent to accept HPV vaccination among mothers may be moderated by sociodemographics.

We assessed differences in response to a tailored recommendation intervention for HPV vaccine by participants' sociodemographic characteristics in this exploratory sub-analysis of a larger web-based, randomized-controlled trial on tailored messaging among mothers with low intent to vaccinate their 11-14-year-old child against HPV. The intervention consisted of pre-recorded video messages tailored to 1-5 common concerns about HPV vaccine. In these exploratory analyses, we used generalized linear models to assess differences in post-intervention intent across intervention arms, stratified by sociodemographic characteristics among 496 trial participants. We found significantly higher post-intervention intent in the intervention participants versus the control group among mothers: 1) with younger children; 2) with white vs. black children; 3) with Non-Hispanic children; 4) who were younger; 5) with some college or vocational training; with household incomes of ≥$100,000; and 7) with 1-2 children. Our findings of effect modification by certain sociodemographic factors such as age, race/ethnicity, and household income should be considered when designing similar tailored messaging interventions.

Health outcomes coding trends in the US Food and Drug Administration's Sentinel System during transition to International Classification of Diseases-10 coding system: A brief review.

BACKGROUND AND PURPOSE: The transition from International Classification of Diseases, 9th revision, clinical modification (ICD-9-CM) to ICD-10-CM poses a challenge to epidemiologic studies that use diagnostic codes to identify health outcomes and covariates. We evaluated coding trends in health outcomes in the US Food and Drug Administration's Sentinel System during the transition. METHODS: We reviewed all health outcomes coding trends reports on the Sentinel website through November 30, 2019 and analyzed trends in incidence and prevalence across the ICD-9-CM and ICD-10-CM eras by visual inspection. RESULTS: We identified 78 unique health outcomes (22 acute, 32 chronic, and 24 acute or chronic) and 140 time-series graphs of incidence and prevalence. The reports also included code lists and code mapping methods used. Of the 140 graphs reviewed, 81 (57.9%) showed consistent trends across the ICD-9-CM and ICD-10-CM eras, while 51 (36.4%) and 8 (5.7%) graphs showed inconsistent and uncertain trends, respectively. Chronic HOIs and acute/chronic HOIs had higher proportions of consistent trends in prevalence definitions (83.9% and 78.3%, respectively) than acute HOIs (28.6%). For incidence, 55.6% of acute HOIs showed consistent trends, while 41.2% of chronic HOIs and 39.3% of acute/chronic HOIs showed consistency. CONCLUSIONS: Researchers using ICD-10-CM algorithms obtained by standardized mappings from ICD-9-CM algorithms should assess the mapping performance before use. The Sentinel reports provide a valuable resource for researchers who need to develop and assess mapping strategies. The reports could benefit from additional information about the algorithm selection process and additional details on monthly incidence and prevalence rates. KEY POINTS: We reviewed health outcomes coding trends reports on the US FDA Sentinel website through November 30, 2019 and analyzed trends in incidence and prevalence across the International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) and ICD-10-CM eras by code mapping method and the type of health outcomes of interest (acute, chronic, acute or chronic). More than a third of the 140 time-series graphs of incidence and prevalence of health outcomes showed inconsistent or uncertain trends. Consistency in trends varied by code mapping method, type of health outcomes of interest, and whether the measurement was incidence or prevalence. Studies using ICD-9-CM-based algorithms mapped to ICD-10-CM codes need to assess the performance of the mappings and conduct manual refinement of the algorithms as needed before using them.

Developing algorithms for identifying major structural birth defects using automated electronic health data.

PURPOSE: Given the 2015 transition to International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic coding, updates to our previously published algorithms for major structural birth defects (BDs) were necessary. Aims of this study were to update, validate, and refine algorithms for identifying selected BDs, and then to use these algorithms to describe BD prevalence in the vaccine safety datalink (VSD) population. METHODS: We converted our ICD-9-CM list of selected BDs to ICD-10-CM using available crosswalks with manual review of codes. We identified, chart reviewed, and adjudicated a sample of infants in the VSD with ≥2 ICD-10-CM diagnoses for one of seven common BDs. Positive predictive values (PPVs) were calculated; for BDs with suboptimal PPV, algorithms were refined. Final automated algorithms were applied to a cohort of live births delivered 10/1/2015-9/30/2017 at eight VSD sites to estimate BD prevalence. This research was approved by the HealthPartners Institutional Review Board, by all participating VSD sites, and by the CDC, with a waiver of informed consent. RESULTS: Of 573 infants with ≥2 diagnoses for a targeted BD, on adjudication, we classified 399 (69.6%) as probable cases, 31 (5.4%) as possible cases and 143 (25.0%) as not having the targeted BD. PPVs for the final BD algorithms ranged from 0.76 (hypospadias) to 1.0 (gastroschisis). Among 212 857 births over 2 years following transition to ICD-10-CM coding, prevalence for the full list of selected defects in the VSD was 1.8%. CONCLUSIONS: Algorithms can identify infants with selected BDs using automated healthcare data with reasonable accuracy. Our updated algorithms can be used in observational studies of maternal vaccine safety and may be adapted for use in other surveillance systems.

Tailored Messages Addressing Human Papillomavirus Vaccination Concerns Improves Behavioral Intent Among Mothers: A Randomized Controlled Trial.

PURPOSE: The aim of the study was to determine whether supplementing a bundled recommendation (recommendation for all 11- to 12-year-old platform vaccines) with tailored messaging that addressed one versus all parental concerns improved human papillomavirus (HPV) vaccination intent among mothers. METHODS: We conducted a Web-based randomized controlled trial, randomizing mothers who did not intend to vaccinate their 11- to 14-year-old child against HPV to (1) bundled recommendation video ("control"); (2) control + video addressing the top HPV vaccine concern; or (3) control + ≥1 videos addressing all concerns. Outcomes were HPV vaccination intent (1 = extremely unlikely and 10 = extremely likely) and strength of main concern (1 = a little concerned and 10 = very concerned). We assessed differences in intervention effects using generalized linear models for vaccine intent and mixed models for the strength of main concern. RESULTS: Of the 762 mothers, 51% had a female child, 82% of children were white, and 90% were non-Hispanic. The mean intent to vaccinate postintervention ranged from 3.5 (95% confidence interval [CI] = 3.1-3.8) in the control group to 4.2 (95% CI = 3.9-4.6) in the all-concerns group (p = .01). The mean strength of the concerns declined pre- to postintervention by .1 (95% CI = -.1 to .3) in the control group (p = .42), .6 (95% CI = .4-.9) in the top concern group (p < .001), and .7 (95% CI = .5-1.0) in the all-concerns group (p < .001). However, the mean strength of the main concerns postintervention remained high (≥7.0 for each group). CONCLUSIONS: Tailored messages addressing all concerns improved HPV vaccination intent and reduced the strength of the main concern more than bundled messages alone, but intent remained low and strength of the main concerns remained high in this vaccine-hesitant population.

Geographic Variation in Pneumonia and Influenza in Long-Term Care Facilities: A National Study.

There is large county-level geographic variation in pneumonia and influenza hospitalizations among short-stay and long-stay long-term care facility residents in the United States. Long-term care facilities in counties in the Southern and Midwestern regions had the highest rates of pneumonia and influenza from 2013 to 2015. Future research should identify reasons for these geographic differences.

Use of Sodium-Glucose Cotransporter 2 Inhibitors in Patients With Type 1 Diabetes and Rates of Diabetic Ketoacidosis.

OBJECTIVE: To estimate real-world off-label use of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 1 diabetes, estimate rates of diabetic ketoacidosis (DKA), and compare them with DKA rates observed in sotagliflozin clinical trials. RESEARCH DESIGN AND METHODS: We identified initiators of SGLT2 inhibitors in the Sentinel System from March 2013 to June 2018, determined the prevalence of type 1 diabetes using a narrow and a broad definition, and measured rates of DKA using administrative claims data. Standardized incidence ratios (SIRs) were calculated using age- and sex-specific follow-up time in Sentinel and age- and sex-specific DKA rates from sotagliflozin trials 309, 310, and 312. RESULTS: Among 475,527 initiators of SGLT2 inhibitors, 0.50% and 0.92% met narrow and broad criteria for type 1 diabetes, respectively. Rates of DKA in the narrow and broad groups were 7.3/100 person-years and 4.5/100 person-years, respectively. Among patients who met narrow criteria for type 1 diabetes, rates of DKA were highest for patients aged 25-44 years, especially females aged 25-44 years (19.7/100 person-years). More DKA events were observed during off-label use of SGLT2 inhibitors in Sentinel than would be expected based on sotagliflozin clinical trials (SIR = 1.83; 95% CI 1.45-2.28). CONCLUSIONS: Real-world off-label use of SGLT2 inhibitors among patients with type 1 diabetes accounted for a small proportion of overall SGLT2 inhibitor use. However, the risk for DKA during off-label use was notable, especially among young, female patients. Although real-word rates of DKA exceeded the expectation based on clinical trials, results should be interpreted with caution due to differences in study methods, patient samples, and study drugs.

Understanding utilization patterns of biologics and biosimilars in the United States to support postmarketing studies of safety and effectiveness.

PURPOSE: To describe utilization of filgrastim and infliximab, the first two products with biosimilars approved in the United States. METHODS: We identified use of filgrastim (reference, tbo-filgrastim, and filgrastim-sndz) and infliximab (reference, infliximab-dyyb, and infliximab-abda) in the Sentinel Distributed Database using Healthcare Common Procedure Coding System (HCPCS) codes and National Drug Codes (NDCs) from January 2015 to August 2018. We calculated the proportion of use by code type and assessed uptake over time. We compared baseline patient characteristics and treatment indications. Among patients with >1 exposure episode, we characterized gaps between episodes. RESULTS: Use was identified primarily via HCPCS codes (filgrastim: 86.4%-97.7%; infliximab: 87.8%-100%) although some was identified via NDCs (filgrastim: 2.2%-13.5%; infliximab: <0.1%-6.5%). Filgrastim reference product use declined from 89.4% in January 2015 to 30.3% in June 2018, with corresponding increases in filgrastim-sndz (0% to 49.3%) and tbo-filgrastim (10.6% to 20.4%). Infliximab biosimilar uptake was low (9.7% in June 2018). We identified 94 846 filgrastim reference product, 27 143 tbo-filgrastim, and 38 264 filgrastim-sndz users. For infliximab, we identified 125 412 reference product, 1034 infliximab-dyyb, 49 infliximab-abda, and 4855 undetermined biosimilar users. Patients receiving filgrastim products were largely similar, but differences in age, sex, and indication were observed across infliximab product users. The median exposure episode gap ranged from 1 to 3 days for filgrastim and 48 to 50 days for infliximab. CONCLUSION: Use of biosimilar filgrastim has increased in the United States, but infliximab biosimilar use remains low. Data on identification of biosimilars in claims data and observed gaps between exposure episodes can be used to support drug safety studies of biosimilars.

Incidence of statin use in older adults with and without cardiovascular disease and diabetes mellitus, January 2008- March 2018.

BACKGROUND: Data from randomized controlled trials and observational studies on older adults who take statins for primary prevention of atherosclerotic cardiovascular disease are limited. To determine the incidence of statin use in older adults with and without cardiovascular disease (CVD) and/or diabetes (DM), we conducted a descriptive observational study. METHODS: The cohort consisted of health plan members in the NIH Collaboratory Distributed Research Network aged >75 years who had continuous drug and medical benefits for ≥183 days during the study period, January 1, 2008- March 31, 2018. We defined DM and CVD using diagnosis codes, and identified statins using dispensing data. Statin use was considered incident if a member had no evidence of statin exposure in the claims during the previous 183 days, and the use was considered long-term if statins were supplied for ≥180 days. Incidence rates were reported among members with and without CVD and/or diabetes, and stratified by year, sex, and age group. RESULTS: Among 757,569 eligible members, 109,306 older adults initiated statins and 54,624 became long-term users. Health plan members with CVD had the highest incidence of statin use (143.9 initiators per 1,000 member-years for CVD & DM; 114.5 initiators per 1,000 member-years for CVD & No DM). Among health plan members without CVD, those with DM had rates of statin use that were over two times higher than members without DM (76.1 versus 34.5 initiators per 1,000 member-years, respectively). Statin initiation remained steady throughout 2008-2016, was slightly higher in males, and declined with increasing age. CONCLUSION: Incidence of statin use varied by CVD and DM comorbidity, and was lowest among those without CVD. These results highlight the potential clinical equipoise to conduct large pragmatic clinical trials to generate evidence that could be used to inform future blood cholesterol guidelines.

Descriptive Analysis of Long- and Intermediate-Acting Insulin and Key Safety Outcomes in Adults with Type 2 Diabetes Mellitus.

BACKGROUND: As new biosimilar and follow-on insulins enter the market, more data are needed on safety, effectiveness, and patterns of use for these products to inform prescriber and patient decision-making regarding treatment. Additionally, data are needed regarding real-world patterns of use to inform future studies comparing the safety and effectiveness of bio-similars to already approved agents for diabetes treatment. OBJECTIVE: To analyze the medication use patterns, adverse events, and availability of glycated hemoglobin (A1c) values for adult patients with type 2 diabetes mellitus (T2DM) who use long-acting insulin (LAI) or neutral protamine Hagedorn (NPH), an intermediate-acting insulin. METHODS: We used the Biologics and Biosimilars Collective Intelligence Consortium's (BBCIC) distributed research network (DRN) for this descriptive analysis. The analysis time frame was January 1, 2011, to September 30, 2015, and included patients continuously insured for at least 183 days before the first date of a filled prescription for LAI or NPH insulin alone or with rapid- or short-acting insulin or sulfonylureas, whether newly starting insulin or switching to a different product. Insulin exposure episodes were the unit of analysis, and patients were classified in cohorts according to treatment. We followed patients until end of health plan enrollment or the end of the study period. We used occurrence of a study outcome, switch to another medication regimen, discontinuation of the current medication, or study end date to mark the end of an insulin episode. We describe demographics and availability of A1c values for analysis. Study outcomes included severe hypoglycemic events and major adverse cardiac events (MACE). RESULTS: We identified 103,951 patients with T2DM from a database of 39.1 million patients with commercial or Medicare Advantage pharmacy and medical benefits, who contributed 279,533 unique insulin exposure episodes. Most episodes (89%) included patients using LAI, and 52% of patients contributed data to 2 or more exposure cohorts. Insulin episodes lasted an average of 3.5 months, and patients had an average follow-up of 8.6 months. The unadjusted rate of severe hypoglycemic events requiring medical attention was 96.9 per 10,000 patient-years at risk (10kPYR). The unadjusted incident MACE rate was 676.9 events per 10kPYR. 38,330 T2DM patients in the BBCIC DRN had a baseline A1c available, and of those, less than 50% had a follow-up A1c result. CONCLUSIONS: Among patients with T2DM, our observed insulin patterns of use and rates of severe hypoglycemic outcomes and MACE are consistent with other studies. We noted a paucity of A1c results available, which implies that additional data sources may be needed to augment the BBCIC DRN. DISCLOSURES: This study was coordinated and funded by the Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) and represents the independent findings of the BBCIC Insulins Principal Investigator and the BBCIC Insulins Research Team. Lockhart is employed by the BBCIC and the Academy of Managed Care Pharmacy (AMCP). Eichelberger was employed by the BBCIC and AMCP at the time of this study. McMahill-Walraven is employed by Aetna, a CVS Health business. Panozzo, Marshall, and Brown are employed by Harvard Pilgrim Healthcare Institute. Aetna was reimbursed for data and analytic support from Harvard Pilgrim Healthcare Institute and the Reagan Udall Foundation for the U.S. Food and Drug Administration. Aetna receives external funding through research grants and subcontracts with Harvard Pilgrim Healthcare Institute, which are funded by the FDA, NIH, PCORI, BBCIC, Pfizer, and GSK; the Reagan-Udall Foundation for IMEDS; and PCORI for the ADAPTABLE Study. This work was previously presented as a poster at AMCP Nexus 2018; October 22-25, 2018; in Orlando, FL.

Harnessing the Biologics and Biosimilars Collective Intelligence Consortium to Evaluate Patterns of Care.

INTRODUCTION: As clinical trials test efficacy rather than effectiveness of medications, real-world effectiveness data often vary from clinical trial data. Given the recent market entry of multiple biologics and biosimilars, a dedicated assessment of these diverse agents is needed to build the evidence base regarding efficacy and safety of innovator biologics and biosimilars. PROGRAM DESCRIPTION: The Academy of Managed Care Pharmacy's Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) was convened to address the lack of real-world, postmarket outcome evidence generation for innovator biologics and corresponding biosimilars. The BBCIC is a multistakeholder scientific research consortium whose participants prioritize topics and collaboratively conduct research studies. The BBCIC conducts a wide range of analyses, including population characterization, epidemiologic studies, and active observational studies, and develops best practices for conducting large-scale studies to provide real-world evidence. OBSERVATIONS: Over the past 3 years, we undertook multiple descriptive analyses with the goal of characterizing data availability and demonstrating the feasibility and efficacy of using the BBCIC distributed research network (DRN), which includes commercial claims data from 2008-2018 covering approximately 100 million lives, with approximately 20 million active members in 2017 from 2 major U.S. health plans and 3 regional integrated delivery networks. We analyzed 4 medication classes of particular interest to biologics and biosimilars development: insulins, granulocyte colony-stimulating factors, erythropoietic-stimulating agents, and anti-inflammatories. We were able to identify exposures and user characteristics in all 4 categories. Herein we describe the successes and challenges of conducting some of our analyses, specifically among insulin users with type 1 diabetes mellitus. IMPLICATIONS: Our results demonstrate the BBCIC DRN's ability to identify and characterize exposures, cohorts, and outcomes that can contribute to more sophisticated comparative surveillance of biosimilars and innovator biologics in the future. Additional linkages to laboratory data and a wider range of insurance carriers will further strengthen the BBCIC DRN. DISCLOSURES: This study was coordinated and funded by the Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) and represents the independent findings of the BBCIC Insulins Principal Investigator and the BBCIC Insulins Research Team. Lockhart is employed by the BBCIC; Eichelberger was employed by the BBCIC at the time of this study. McMahill-Walraven is employed by Aetna, a CVS Health business. Panozzo, Marshall, and Brown are employed by Harvard Pilgrim Healthcare Institute. Aetna receives external funding through research grants and subcontracts with Harvard Pilgrim Healthcare Institute, which are funded by the FDA, NIH, PCORI, BBCIC, Pfizer, and GSK; the Reagan-Udall Foundation for IMEDS; and PCORI for the ADAPTABLE Study. Aetna was reimbursed for data and analytic support from Harvard Pilgrim Healthcare Institute and the Reagan Udall Foundation for the U.S. Food and Drug Administration. This work was presented as a poster at AMCP Nexus 2018; October 22-25, 2018; in Orlando, FL.

Associations between HPV vaccination among women and their 11-14-year-old children.

The human papillomavirus (HPV) vaccine has been available in the United States for over a decade. We sought to examine the associations between self-reported receipt of HPV vaccination among women and their 11-14-year-old children in 27 low-coverage states. Among the 3,261 mothers we surveyed, 18% reported receiving ≥1 dose of HPV vaccine. A significantly higher proportion of vaccinated women reported vaccination of their children compared to unvaccinated women (83% vs. 56%, p < .001). In multivariable logistic regression, vaccinated women (vs. unvaccinated) had 3.58 (95% CI: 2.81-4.56) times the adjusted-odds of vaccinating their children (≥1 dose HPV vaccine). Among unvaccinated children, vaccinated mothers (vs. unvaccinated) had 3.32 (95% CI: 2.09-5.26) times the adjusted odds of high intention to vaccinate their children in the next 12 months. We did not observe associations between mothers' vaccination confidence and their vaccination status. We conclude that mothers who received ≥1 dose of HPV vaccine may be more likely to initiate or highly intend to initiate the HPV vaccine series for their children. This may have important implications for meeting population goals for HPV vaccination coverage as an increasing proportion of mothers are likely to be vaccinated over time.